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Completed

NCT Number: NCT05079919

A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia

The purpose of the study is to evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.

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Key information

Conditions

Severe Hypertriglyceridemia Dyslipidemias Hyperlipidemias Hypertriglyceridemia Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

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About this study

This is a multi-center, randomized, double-blind, placebo-controlled study in 617 participants. Participants will be randomized to receive olezarsen or placebo in a 53-week treatment period. The length of participation in the study will be approximately 78 weeks, which includes an up to 12-week screening period, a 53-week treatment period, and a 13-week post-treatment evaluation period or transition to open-label extension (OLE) study with up to 1-year treatment.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification
  • Patients must be on lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study.

Key Exclusion Criteria:

  • Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
  • Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal
  • Total bilirubin > upper limit of normal unless due to Gilbert's syndrome
  • Estimated GFR < 30 mL/min/1.73 m^2

Treatment and study plan

Olezarsen

Drug

Olezarsen will be administered by SC injection.

Other names: AKCEA-APOCIII-LRx, ISIS 678354

Placebo

Drug

Olezarsen-matching placebo will be administered by SC injection.

Primary outcomes

  1. Percent Change from Baseline in Fasting TG Compared to Placebo

    Time frame: Baseline and Month 6

Secondary outcomes

  1. Percent Change from Baseline in Fasting TG Compared to Placebo

    Time frame: Baseline and Month 12

  2. Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III), Remnant Cholesterol and Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) Compared to Placebo

    Time frame: Baseline, Month 6 and 12

  3. Proportion of Patients Who Achieve Fasting TG <500 mg/dL (5.65 mmol/L) Compared to Placebo

    Time frame: Month 12

  4. Proportion of Participants Who Achieve Fasting TG < 880 mg/dL (10 mmol/L) Compared to Placebo in the Subgroup of Participants with Baseline TG ≥ 880 mg/dL

    Time frame: Month 12

  5. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo

    Time frame: Week 1 through Week 53

  6. Absolute Change in Hepatic Fat Fraction (HFF) Between Olezarsen Treatment Group and Pooled Placebo

    Time frame: Baseline through Month 12

Sponsors and collaborators

Lead sponsor

Ionis Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 678354 Administered Subcutaneously to Patients With Severe Hypertriglyceridemia

Important dates

Study start
2021
Primary completion
2024
Study completion
2025
First posted
Oct 15, 2021
Registry last updated
Feb 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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